The transcriptional response of mammalian cancer cells to irradiation is dominated by a cell cycle signature which is strongly attenuated in non-cancer cells and tissues

Abstract

Purpose: Our goal was to identify genes showing a general transcriptional response to irradiation in mammalian cells and to analyze their response in function of dose, time and quality of irradiation and of cell type.

Materials and methods: We used a modified MIAME (Minimal Information About Microarray Experiments) protocol to import microarray data from 177 different irradiation conditions in the Radiation Genes database and performed cut-off-based selections and hierarchical gene clustering.

Results: We identified a set of 29 genes which respond to a wide range of irradiation conditions in different cell types and tissues. Functional analysis of the negatively modulated genes revealed a dominant signature of mitotic cell cycle regulation which appears both dose and time-dependent. This signature is prominent in cancer cells and highly proliferating tissues but it is strongly attenuated in non cancer cells.

Conclusions: The transcriptional response of mammalian cancer cells to irradiation is dominated by a mitotic cell cycle signature both dose and time-dependent. This core response, which is present in cancer cells and highly proliferating tissues such as skin, blood and lymph node, is weaker or absent in non-cancer cells and in liver and spleen. CDKN1A (cyclin-dependent kinase inhibitor 1A) appears as the most generally induced mammalian gene and its response (mostly dose- and time-independent) seems to go beyond the typical DNA damage response.

Keywords::

• Gene expression
• radiation
• cell cycle signature

Acknowledgements

The work was partially funded by ASI (Agenzia Spaziale Italiana) MoMa program ‘From Molecules to Man: Space Research Applied to the improvement of the Quality of Life of the Ageing Population on Earth’ grant.